January 09, 2018 - Notice of Plans to Allow 13 NIDA Program Announcements to Expire Without Renewal and Guidance to Applicants on how to Apply for Research Grants in Those Topic Areas. See Notice NOT-DA-17-065.

May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018. See NOT-OD-17-062.

This Funding Opportunity Announcement (FOA) encourages exploratory/developmental
grant (R21) applications from institutions and organizations that propose to
study the effects and functional consequences of cannabis and cannabinoid
exposures on the developing brain, from pre-, peri-, post-natal development
through young adulthood in animal models and humans. Topics of interest
pertaining to this PA include, but are not limited to: molecular and cellular
mechanisms of cannabis/cannabinoid effects on the developing brain; long term
functional consequences of cannabis/cannabinoid exposure on learning and
memory, cognitive and emotional development.

Key Dates

Posted Date

March 26, 2014

Open Date (Earliest Submission Date)

May 16, 2014

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Standard
dates apply, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

New Date January 8, 2018 per issuance of NOT-DA-17-017. (Original Expiration Date: May 8, 2017)

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any program-specific
instructions noted in Section IV. When
the program-specific instructions deviate from those in the Application Guide,
follow the program-specific instructions. Applications that do not
comply with these instructions may be delayed or not accepted for review.

Note: This Exploratory/Developmental Grant (R21) FOA,
accompanying the Research Project Grant (R01) FOA, PA-14-162, solicits two-year
research project applications for the studies of effects of cannabis use and
cannabinoids on the developing brain. Exploratory/developmental applications
are encouraged to test novel scientific ideas, emerging new hypotheses or model
systems, and develop tools and technologies that have the potential for
significant impact on the effects of cannabis use and cannabinoids on the
developing brain. An R21 grant application need not have preliminary data, but
should reflect high-risk-high-impact qualities. The goal of this FOA is to
accelerate early stage development of promising concepts, hypotheses and
facilitate the progress in overcoming technical challenges.

NIDA supports research to understand, prevent, and treat
substance use disorders and mitigate their consequences to improve the public’s
health. Current epidemiological survey data on cannabis and cannabinoids use
among adolescents over the last five-years show significant increases in past-year
and past-month (current) cannabis use across 8th, 10th and 12th grades. And
rates of daily or nearly daily cannabis and cannabinoids use among 12th graders
are at 6.5%. These increases parallel softening attitudes about the perceived
risk of harm and disapproval associated with cannabis and cannabinoid use.
These data, coupled with evolving policies on cannabis and cannabinoid use are
likely to impact the use of cannabis and cannabinoids by different segments of
the population (especially youth), strengthening the need to fully understand
and address the potential risks of exposure. Particularly important is
understanding how and when the brain is most vulnerable to insult or injury,
e.g., during fetal development, childhood, and adolescence—periods of active
maturation. Information from animal models as well as human studies is needed
on the impact of chronic, as well as acute, cannabis/cannabinoid exposure on a
variety of outcomes, spanning molecular, cellular, and neurobiological
approaches; brain imaging (e.g., anatomy and connectivity); and behavior.

Exposure to cannabis and cannabinoids during prenatal,
perinatal, postnatal, childhood and adolescent development may produce enduring
neurobiological and neurodevelopmental effects that could have wide-ranging
impact extending into adulthood, including the possibility of cognitive
impairments and heightened vulnerability to drug addiction. In animal models,
early (i.e., prenatal, postnatal, adolescent) cannabis exposure leads to
specific neuronal alterations, especially in the nucleus accumbens
enkephalin/D2 striatopallidal neurons, as well as dysregulation of repressive
epigenetic marks, and impaired synaptic plasticity, and these may translate to
altered behavioral endpoints, such as increased impulsivity, among others.

Yet, in humans, both cannabis and cannabidiol (CBD; one of
~85 cannabinoids found in cannabis) have been suggested as treatments for a
variety of indications, without a detailed understanding of either their
beneficial or adverse effects, especially on the developing (and vulnerable)
brain. Given that some states have legalized the use of cannabis for medical
or recreational purposes, a better understanding of how cannabis and its
components affect brain function, especially during neurodevelopmental periods,
is warranted. We would expect there to be different effects of
cannabis/cannabinoid exposure based on the precise timing (e.g., developmental
stage), frequency of exposure, dosages, constituent(s) etc; therefore, experiments
designed to address these aspects are of interest.

Purpose and
Objectives

The purpose of this FOA is to support research that will
examine whether chronic, intermittent and/or acute exposure to cannabis and
cannabinoids (e.g., delta9-THC, cannabidiol) during active periods of brain
development (e.g., fetal, adolescent) can cause long term changes in brain
function. Emerging evidence suggests that THC exposure leads to a spectrum of
behavioral effects, dependent on age, sex/gender, genetic, and environmental
factors (and their interactions). However, there are surprisingly few basic
research studies assessing cannabinoid exposure on neurodevelopment or
neurobiology and the impact on subsequent behavioral or biological outcomes.

Studies in humans have suggested adverse psychiatric,
cognitive, and behavioral consequences of cannabis use in both adults and
children, often dependent on time of exposure; frequency of use; and genetic or
other factors. For example, early and frequent cannabis use has been associated
with decreases in IQ, heightened risk of substance abuse in later life, and
psychiatric disorders in genetically vulnerable individuals. Most of these
findings come from epidemiological studies conducted in humans, which are by
their nature, observational and correlational, making it difficult to attribute
causality to reported consequences of cannabis exposure. Thus, research is
needed to provide a deeper mechanistic and causal understanding of cannabis’
effects.

Neurocognitive assessments along with functional
neuroimaging measures, such as task-based fMRI, resting-state fMRI, as well as
positron emission tomography (PET) indicate that cannabis/cannabinoid use and
abuse can alter brain activity, executive function, intelligence, and possibly
risky behavior and impulsivity. Similarly, findings from other animal and
human studies have reinforced that cannabis and cannabinoid exposure is
associated with defective neurogenesis in hippocampus and reduction of
hippocampal and amygdaloidal volume, respectively. Since the endocannabinoid
system is involved in neurogenesis, neuronal migration, axon guidance, and
synaptic plasticity, research is needed to understand the biologic and
neurobehavioral consequences of cannabis exposure on brain function.

While research to understand the long-term neurobehavioral
consequences of early exposure is important, there is also a need to better
understand the neurobiology of the rewarding or reinforcing effects of specific
cannabinoids in cannabis, especially ?9-THC. Animal models of
self-administration are lacking and this is a current challenge in the field.
Prior studies of experimenter-administered THC (i.e., passive exposure) do not
model drug-taking or seeking behavior in the human user. Moreover, much prior
research has been conducted with THC concentrations that may not adequately
reflect the potency and constituency of cannabis/cannabinoids used today.
Animal models need to be developed so that higher potency cannabis/cannabinoids
can be used to explore questions, such as effects on cognition, emotion, and
motivation over the course of prenatal, adolescent and young adulthood
development.

Studies of sex/gender specific outcomes that show
differences in brain morphology, age-dependent changes in cannabinoid receptor
binding, pharmacokinetics, pharmacodynamics, and variation of behaviors such as
acquisition, withdrawal, reinstatement of cannabinoids dependence and effects
on learning and memory should be expanded as applicable.

The research areas of interest of this FOA include, but are
not limited to the following:

Animal or Human Research on the Impact of Cannabis and
Cannabinoids on the Developing Brain, such as:

The cellular and molecular mechanisms of cannabis or cannabinoid
exposure on known and yet to be discovered endocannabinoid and cannabinoid
receptor signaling in neurogenesis, migration, and neuronal and glial
differentiation

Identification and characterization of single nucleotide
polymorphisms of cannabinoid receptors, FAAH, co-activators and other molecules,
known or to be identified, that affect physiology in the presence of cannabis
and cannabinoids

Impact of exposure on brain energetics and metabolism during
development

Changes in brain structure and dynamic activity as a function of
cannabis/cannabinoids use, either alone or more commonly in conjunction with
other substances (i.e. nicotine, alcohol)

Molecular imaging of changes in gene expression and epigenetic
factors as the consequence of cannabis and cannabinoid exposure in the
developing brain

Research to identify and characterize the behavioral consequences
of genetic, cellular and neuroanatomical changes induced by cannabis/cannabinoids
exposure during development, such as:

Effects
of early cannabis and cannabinoid exposures on critical aspects of cognitive
processes (attention, memory, decision-making, impulsivity, etc.) in later life

Effects
of cannabinoids, especially ?9-THC, on cognitive, emotional and
motivational processes at different stages of development

Vulnerability
changes produced by early life cannabis/cannabinoid exposure, on subsequent
drug sensitivity or the motivation for administering ‘other’ drugs of abuse,
and studies on the neurobiological mechanisms for cross-sensitization

Technology and Methods Development for Studying Cannabis and
Cannabinoid Effects

Site and tissue specific gene mutation or knock out of
cannabinoid receptors or co-activators in developing brains in hippocampus,
amygdala and prefrontal cortex for the study of roles of endocannabinoids as
well as consequences of cannabinoid exposure

Development of methods for assessing self-administration of ?9-THC
and cannabis smoke of various cannabinoid compositions

Note: For functional genomics studies of cannabis and
cannabinoid effects and consequences, applicants are encouraged to respond to PA-14-014 "Functional Genetics, Epigenetics, and Non-coding RNAs in Substance Abuse
(R01)".

Animals should be assigned randomly to the various experimental
groups, and the method of randomization reported.

Data should be collected and processed randomly or appropriately
blocked.

Blinding

Allocation concealment: the investigator should be unaware of the
group to which the next animal taken from a cage will be allocated.

Blinded conduct of the experiment: animal caretakers and investigators
conducting the experiments should be blinded to the allocation sequence.

Blinded assessment of outcome: investigators assessing, measuring
or quantifying experimental outcomes should be blinded to the intervention.

Sample-size estimation

An appropriate sample size should be computed when the study is
being designed and the statistical method of computation reported.

Statistical methods that take into account multiple evaluations
of the data should be used when an interim evaluation is carried out.

Data handling

Rules for stopping data collection should be defined in advance.

Criteria for inclusion and exclusion of data should be
established prospectively.

How outliers will be defined and handled should be decided when
the experiment is being designed, and any data removed before analysis should
be reported.

The primary end point should be prospectively selected. If
multiple end points are to be assessed, then appropriate statistical
corrections should be applied.

Investigators should report on data missing because of attrition
or exclusion.

Pseudo replicate issues need to be considered during study design
and analysis.

Investigators should report how often a particular experiment was
performed and whether results were substantiated by repetition under a range of
conditions.

Special
Considerations

HIV/AIDS Counseling and Testing Policy for the National
Institute on Drug Abuse: In light of recent significant advances in rapid
testing for HIV and in effective treatments for HIV, NIDA has revised its 2001
policy on HIV counseling and testing. NIDA-funded researchers are strongly
encouraged to provide and/or refer research subjects to HIV risk reduction
education and education about the benefits of HIV treatment, counseling and
testing, referral to treatment, and other appropriate interventions to prevent
acquisition and transmission of HIV. This policy applies to all NIDA funded
research conducted domestically or internationally. For more information see https://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended
Guidelines for the Administration of Drugs to Human Subjects: The National
Advisory Council on Drug Abuse (NACDA) recognizes the importance of research
involving the administration of drugs with abuse potential, and dependence or
addiction liability, to human subjects. Potential applicants are encouraged
to obtain and review these recommendations of Council before submitting an
application that will administer compounds to human subjects. The guidelines
are available on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Data Harmonization for Substance Abuse and Addiction via the
PhenX Toolkit: NIDA strongly encourages investigators involved in
human-subjects studies to employ a common set of tools and resources that will
promote the collection of comparable data across studies and to do so by
incorporating the measures from the Core and Specialty collections, which are
available in the Substance Abuse and Addiction Collection of the PhenX Toolkit
(www.phenxtoolkit.org). Please see NOT-DA-12-008 for further details.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or
both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New
Resubmission
Revisions

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations
and the submission of a sufficient number of meritorious applications.

Award Budget

Direct costs are limited to $275,000 over an R21 two-year
period, with no more than $200,000 in direct costs allowed in any single year.

Award Project Period

The maximum period is 2 years.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as they
are working through their SAM or Grants.gov registration. eRA Commons requires
organizations to identify at least one Signing Official (SO) and at least one
Program Director/Principal Investigator (PD/PI) account in order to submit an
application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some components
marked optional in the application package are required for submission of
applications for this FOA. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Appendix:
Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions
for completing Planned Enrollment Reports as described in the SF424 (R&R)
Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing Cumulative Inclusion Enrollment Report
as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Important Update: See
NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, note the following:

The R21 exploratory/developmental
grant supports investigation of novel scientific ideas or new model systems,
tools, or technologies that have the potential for significant impact on
biomedical or biobehavioral research. An R21 grant application need not have
extensive background material or preliminary information. Accordingly,
reviewers will focus their evaluation on the conceptual framework, the level of
innovation, and the potential to significantly advance our knowledge or
understanding. Appropriate justification for the proposed work can be provided
through literature citations, data from other sources, or, when available, from
investigator-generated data. Preliminary data are not required for R21
applications; however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers
well suited to the project? If Early Stage Investigators or
those in the early stages
of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves human subjects and/or NIH-defined clinical research,
are the plans to address 1) the protection of human subjects from research
risks, and 2) inclusion (or exclusion) of individuals on the basis of
sex/gender, race, and ethnicity, as well as the inclusion or exclusion of
children, justified in terms of the scientific goals and research strategy
proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Guidelines
for the Review of Human Subjects.

Inclusion of Women, Minorities, and
Children

When the proposed project involves human subjects
and/or NIH-defined clinical research, the committee will evaluate the proposed
plans for the inclusion (or exclusion) of individuals on the basis of
sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of
children to determine if it is justified in terms of the scientific goals and
research strategy proposed. For additional information on review of the
Inclusion section, please refer to the Guidelines
for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet for
Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the
appropriateness of the proposed expansion of the scope of the project. If the
Revision application relates to a specific line of investigation presented in
the original application that was not recommended for approval by the committee,
then the committee will consider whether the responses to comments from the
previous scientific review group are adequate and whether substantial changes
are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the Center for
Scientific Review, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications. Following
initial peer review, recommended applications will receive a second level of
review by the appropriate national Advisory Council or Board. The following
will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH Grants
Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.